GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE309nnn/GSE309474/primary200OKGenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309474GEOGSEfalseHypoxia-driven metabolic reprogramming regulates mouse epiblast development [ATAC-seq]Mouse epiblast development is characterized by extensive cell differentiation and rapid proliferation. However, the metabolic mechanisms supporting these processes remain poorly understood. Here, we demonstrate hypoxia signaling as a key regulator of metabolic reprogramming during mouse epiblast development. Under the hypoxic conditions of implantation, glucose metabolism shifts toward the glycolysis for energy production and the pentose phosphate pathway for biosynthesis in mouse epiblast. Concurrently, glutamine metabolism is markedly enhanced, predominantly through reductive carboxylation, to supply acetyl-CoA for histone acetylation and lipid synthesis, while also providing nitrogen for nucleotide and amino acid production. These metabolic adaptations collectively sustain both the epigenetic regulation of cell fate decision and the biosynthetic requirements of rapidly proliferating epiblast cells. Disruption of glutamine metabolism, hypoxia signaling, or lipid synthesis compromises epiblast proliferation and chromatin remodeling. Together, our findings delineate a hypoxia-driven metabolic framework essential for mouse early post-implantation epiblast development, wherein glutamine metabolism as an indispensable signaling coordinating anabolic and epigenetic programs to support epiblast growth and lineage specification.2026/09/29GSE309474GSM9267903GSM9267902GSM9267905GSM9267904GSM9267907GSM9267906GSM9267901GSM926790034290309474Mus musculus